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首页> 外文期刊>Biomaterials >An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography
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An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography

机译：基于Gd（DO3A-Lys）的血管内MRI造影剂用于肿瘤血管造影

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An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3T, 7T and 9.4T magnetic fields. The relaxivity-dependent albumin binding study indicated that Gd(DO3A-Lys) partially bound to albumin protein. Invitro cell viability in HK2 cell indicated low cytotoxicity of Gd(DO3A-Lys) up to 1.2mm [Gd] concentration. Invivo toxicity studies demonstrated no toxicity of Gd(DO3A-Lys) on kidney tissues up to 0.2mm [Gd]. While the toxicity on liver tissue was not observed at low dosage (1.0mm [Gd]), Gd(DO3A-Lys) cause certain damage on hepatic tissue at high dosage (2.0mm [Gd]). The DO3A-Lys has been labeled with 68Ga radioisotope for biodistribution studies. 68Ga(DO3A-Lys) has high uptake in both HT1080 and U87MG xenograft tumors, and has high accumulation in blood. Contrast-enhanced MR angiography (CE-MRA) in mice bearing U87MG xenograft tumor demonstrated that Gd(DO3A-Lys) could enhance vascular microenvironment around the tumor, and displays promising characteristics of an MRI contrast agent for tumor angiography.
机译：血管内MRI造影剂Gd（DO3A-Lys），Ga（III）（2,2'，2''-（10-（3-（5-苯甲酰胺-6-甲氧基-6-氧己基氨基）-3-氧丙基）- 1,4,7,10-四氮杂十二环十二烷-1,4,7-三基）三乙酸酯已被研究用于肿瘤血管造影，基于其高松弛性和长的血液半衰期。造影剂的制备程序已进行了修改，以实现更高的收率并提高合成的可重复性。 Gd（DO3A-Lys）的高弛豫性已通过在3T，7T和9.4T磁场下的测量得到证实。松弛依赖性白蛋白结合研究表明，Gd（DO3A-Lys）部分结合白蛋白。 HK2细胞中的体外细胞生存能力表明，高达1.2mm [Gd]浓度的Gd（DO3A-Lys）细胞毒性较低。体内毒性研究表明，Gd（DO3A-Lys）对高达0.2mm [Gd]的肾脏组织无毒性。低剂量（1.0mm [Gd]）未观察到对肝组织的毒性，高剂量（2.0mm [Gd]）下，Gd（DO3A-Lys）对肝组织造成一定损害。 DO3A-Lys已被68Ga放射性同位素标记，用于生物分布研究。 68Ga（DO3A-Lys）在HT1080和U87MG异种移植肿瘤中均具有较高的摄取，并在血液中具有较高的积累。带有U87MG异种移植肿瘤的小鼠中的造影剂增强MR血管造影（CE-MRA）表明，Gd（DO3A-Lys）可以增强肿瘤周围的血管微环境，并显示出用于肿瘤血管造影的MRI造影剂的良好前景。

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